Generic drug: carbamazepine
Brand name: Carnexiv
What is Carnexiv (carbamazepine), and how does it work?
Carnexiv (carbamazepine) injection is an anticonvulsant indicated as replacement therapy for oral carbamazepine formulations, when oral administration is temporarily not feasible, in adults with the following seizure types:
- partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns which include the above, or other partial or generalized seizures.
What are the side effects of Carnexiv?
Common side effects of Carnexiv include:
- blurred vision,
- double vision,
- infusion-related reaction,
- infusion site pain, and
SERIOUS DERMATOLOGIC REACTIONS and APLASTIC ANEMIA AND AGRANULOCYTOSIS
Serious Dermatologic Reactions and HLA-B*1502 Allele
- Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have occurred in patients treated with carbamazepine.
- There is a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene that is found almost exclusively in patients with Asian ancestry.
- Avoid use of Carnexiv in patients testing positive for the allele unless the benefit clearly outweighs the risk. Discontinue Carnexiv if you suspect that the patient is having a serious dermatologic reaction.
Aplastic Anemia and Agranulocytosis
What is the dosage for Carnexiv?
- Carnexiv is a replacement therapy for oral carbamazepine. Carbamazepine treatment should generally be initiated with an oral carbamazepine formulation.
- The total daily dose of Carnexiv is 70% of the total daily oral carbamazepine dose from which patients are being switched (see Table 1). The total daily dose of Carnexiv should be equally divided in four 30-minute infusions, separated by 6 hours.
- Patients should be switched back to oral carbamazepine administration at their previous total daily oral dose and frequency of administration as soon as clinically appropriate. The use of Carnexiv for periods of more than 7 days has not been studied.
Table 1: Determination of Total Daily Dose for Carnexiv Infusion
|Total Daily Oral Carbamazepine Dose (mg/day)||Corresponding Total Daily Dose of Carnexiv (mg/day)||Dose of Carnexiv to be administered every 6 hours (mg)|
What drugs interact with Carnexiv?
Effects Of Carnexiv On Other Drugs
- Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19 and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by CYP1A2, 2B6, 2C9/19, and 3A4 through induction of their metabolism (see Tables 5 and 6).
Table 5: Effects of Carbamazepine on Other Drugs
|Concomitant Drug Name||Effect of Carbamazepine on Other Drugs||Clinical Recommendation|
|Boceprevir||Decrease in boceprevir levels||Coadministration of carbamazepine with boceprevir is contraindicated|
|Acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine, corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, eslicarbazepine, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide||Decrease in concomitant drug levels||Monitor the concentration and consider a dosage adjustment of the concomitant drug(s)|
|Cyclophosphamide||Increase in cyclophosphamide levels (potential for increased toxicity)||Monitor for signs of increased cyclophosphamide toxicity|
|Aripiprazole||Decrease in aripiprazole levels||When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled; additional dose increases should be based on clinical evaluation; when carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced|
|Tacrolimus||Decrease in tacrolimus levels||Monitor tacrolimus blood concentrations and make appropriate dosage adjustments|
|Temsirolimus||Decrease in temsirolimus levels||The use of concomitant strong CYP3A4 inducers such as carbamazepine should be avoided with temsirolimus; if carbamazepine must be coadministered with temsirolimus, consider adjusting the dosage of temsirolimus|
|Lapatinib||Decrease in lapatinib levels||The use of carbamazepine with lapatinib should generally be avoided; dosage adjustment should be considered if lapatinib is coadministered with carbamazepine; if carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up; if carbamazepine is discontinued, the lapatinib dose should be reduced|
|Nefazodone||Decrease in nefazodone levels||Coadministration of carbamazepine with nefazodone is contraindicated|
|Valproate||Decrease in valproate levels||Monitor valproate concentrations when carbamazepine is introduced or withdrawn in patients using valproic acid|
Table 6: Effects of Carbamazepine on Other Drugs (Continued)
|Concomitant Drug Name||Effect of Carbamazepine on Other Drugs||Clinical Recommendation|
|Lithium||May increase the risk of neurotoxic side effects||Use with intensive monitoring|
|Isoniazid||May increase isoniazid-induced hepatotoxicity|
|Diuretics (e.g., hydrochlorothiazide, furosemide)||May lead to symptomatic hyponatremia|
|Hormonal contraceptives (e.g., oral and levonorgestrel subdermal implant contraceptives)||May render the contraceptives less effective because the plasma concentrations of the hormones may be decreased; breakthrough bleeding and unintended pregnancies have been reported||Consider alternative or back-up methods of contraception|
|Neuromuscular blocking agents (e.g., pancuronium, vecuronium, rocuronium, and cisatracurium)||Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents||Closely monitor patients for more rapid recovery from neuromuscular blockade than expected; infusion rate may need to be higher|
|Direct acting oral anticoagulants (e.g., rivaroxaban, apixaban, dabigatran, and edoxaban)||Decreased plasma concentrations of these anticoagulants that may be insufficient to achieve the intended therapeutic effect||Coadministration with carbamazepine should generally be avoided|
|Delavirdine or other non-nucleoside reverse transcriptase inhibitors (NNRTIs)||Decrease in delavirdine or NNRTI levels||Contraindicated with carbamazepine|
Effects Of Other Drugs On Carnexiv
- CYP3A4 inhibitors inhibit Carnexiv metabolism and can thus increase plasma carbamazepine levels.
- CYP3A4 inducers can increase the rate of Carnexiv metabolism and thus decrease carbamazepine levels (see Table 7).
Table 7: Effects of Other Drugs on Carbamazepine
|Concomitant Drug Name||Effect of Concomitant Drug on Carbamazepine||Clinical Recommendation|
|Aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, delavirdine, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, trazodone, olanzapine, loratadine, terfenadine, omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene, azoles (e.g., ketaconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, protease inhibitors||Increase in carbamazepine level (by CYP3A4 inhibition)||Closely monitor carbamazepine levels; dosage adjustment may be required|
|Cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline||Decrease in carbamazepine level (by CYP3A4 induction)|
|Loxapine, quetiapine and valproic acid||Decrease in carbamazepine level and increase in metabolite (carbamazepine-10,11-epoxide) levels (both by inhibition of human microsomal epoxide hydrolase)||Closely monitor carbamazepine levels; dosage adjustment may be required|
Pharmacodynamic Drug Interactions
Monoamine Oxidase Inhibitors
Is Carnexiv safe to use while pregnant or breastfeeding?
- Pregnancy registry and epidemiological data indicate that carbamazepine can cause fetal harm when administered to a pregnant woman.
- Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information regarding the effects of in utero exposure to Carnexiv. To enroll, patients can call the toll-free number 1-888-233-2334. Information about the North American Antiepileptic Drug Pregnancy Registry can be found at http://www.aedpregnancyregistry.org
- Carbamazepine and its epoxide metabolite are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants exposed to Carnexiv, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
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Migraines are a type of headache and seizures are the main symptom of epilepsy. Migraine headaches and seizures are two different neurological problems that have similar signs, symptoms, and auras, for example, sensitivity to light (photophobia) and sound, irritability, nausea, and vomiting. Symptoms unique to migraine and migraine auras are water retention, problems sleeping, appetite changes, and talkativeness. Symptoms unique to seizure and seizures auras are depression, a feeling of heaviness, a feeling that a seizure is approaching, and depression. Many of the symptoms of migraine and seizures are the same, however, seizures do not cause migraines; however, people who have seizures are twice as likely to have migraines and vice-versa. People who have migraines are twice as likely to have seizures, and people with seizures are twice as likely to have migraines; however, one condition does not cause the other.
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Treatment & Diagnosis
Medications & Supplements
- carbamazepine - oral, Tegretol
- carbamazepine suspension - oral, Tegretol
- carbamazepine chewable tablet - oral, Tegretol
- carbamazepine extended-release - oral, Carbatrol, Tegretol XR
- CARBAMAZEPINE EXTENDED RELEASE TABLETS-ORAL, Tegretol XR
- carbamazepine, Tegretol, Tegretol XR , Equetro, Carbatrol, Epitol, Teril
- Side Effects of Tegretol (carbamazepine)
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